The Case Western Reserve University (CWRU) - Cleveland VA Hospital MHCRC provides core resources and pilot study support for a multidisciplinary study of the biology, phenomenology and classification of schizophrenia and the affective disorders and related basic neuroscience research. The MHCRC is based on three inpatient wards with 52 research beds and outpatient facilities at CWRU and the Cleveland VA. Continuation of clinical research from the Chicago phase of this program by Chicago MHCRC investigators is also an important component of this project. A post-mortem study of suicide is underway and a prospective study of suicidal patients has been initiated. Over 700 inpatients (75-100 per year) have been studied with a standardized, reliable clinical method which includes the Present State Examination or SADS, SADS-Current interviews, a Psychiatric History Schedule, BPRS and Hamilton Depression Rating Scale. Clinical and basic research on the role of serotonin (5HT) and dopamine in affective disorders and schizophrenia and the mechanism of action of antidepressants, ECT, lithium and neuroleptics are the principal components of MHCRC research. The major research goals of the MHCRC are: a) identification of putative biological markers, e.g., platelet 3H-imipramine binding, serotonin uptake and their interrelations; b) investigation of the biological component of the etiology of the major psychoses; c) determining the mechanism of action of psychotropic drugs and ECT; d) development of the neuroendocrine strategy in psychiatry, e.g., 5HT challenge tests and clarifying the biological basis for DST nonsuppression; e) clinical psychopharmacology, e.g., clinical studies of atypical neuroleptic drugs; f) psychopharmacology, e.g., eye tracking studies; g) positron emission tomography; h) magnetic resonance imaging; i) neuropsychological studies; j) psychopathologic studies, e.g. the relation between positive and negative symptoms; and k) follow- up studies of schizophrenia and the affective disorder. In addition to the clinical research studies, the MHCRC carriers out basic research studies in preclinical biochemistry, neuropharmacology and neuroendocrinology which are closely integrated with its clinical research program. Research training is provided to research fellows (M.D., Ph.D., pre-doctoral), psychiatric residents, medical and college students, and visiting scientists.